Adverse Reaction to Oxytocin Clinical Trial
Official title:
Continued Versus Discontinued Oxytocin Stimulation of Labour in a Double-blind Randomised Controlled Trial
Background:
The proposed study will investigate the effect of Syntocinon® (synthetic oxytocin) to induce
labour. The hypothesis to be studied is that once the active phase of labour has commenced,
Syntocinon® can be discontinued and the labour process will continue.
Design:
Double-blind randomised controlled multicentre trial
Setting:
Aarhus University Hospital, Denmark and Regional Hospital of Randers, Denmark
Population:
1200 women (600 in each group) stimulated in the latent phase of labour with oxytocin for
induction
Methods:
The Syntocinon® infusion will be replaced with either continuous isotonic saline (placebo) or
Syntocinon® infusion (control group), when the active phase of labour is reached.
Main outcome measures:
Caesarean section (primary outcome), tachysystole, neonatal asphyxia, birth experience
Perspective:
Syntocinon® is on the list high-alert medications and associated with complications for
mother and child during labour. Reducing the duration of stimulation during labour may lower
the number of asphyxial sequelae and the number of caesarean sections.
Randomisation:
When the orificium ≥6 cm, regular painful contractions (≥3 per 10 minutes) and rupture of
membranes participants will be randomised in a 1:1 ratio to either the control (continued
Syntocinon®) or intervention (discontinued Syntocinon®) group using an Internet-based
randomisation programme. The randomisation can only be performed when the woman consents to
participation. Written consent can be given after the commencement of the Syntocinon®
infusion, provided the woman previously has received sufficient information for her to give
properly informed consent. Random block-sizes of 8 are used, and the participants will be
stratified by site (Aarhus University Hospital, Randers Regional Hospital, Aalborg University
hospital, or Sygehus Lillebælt Kolding), parity (nulliparous or parous) and indication for
Syntocinon® infusion (induction or induction due to premature rupture of membranes).
The randomisation number corresponds to number of the project medicine (ampoule). The
personnel of the delivery ward will administer the ampoules according to existing guidelines
concerning medicine administration
Oxytocin stimulation protocol:
Existing national procedures prior to stimulation will be followed, including use of the
existing checklists. No further examination will be done prior to inclusion and stimulation,
no blood samples nor ECG to identify e.g. unknown QT-syndrome will be performed as this is
never performed as a standard procedure prior to induction.
Latent phase: Stimulation will be given according to national DSOG guidelines7. Initially 20
ml/hour of 10 IE Syntocinon® diluted in 1000 ml 0,9% NaCl. The dose rate will be increased
every 20 minutes by 20 ml/hour until appropriate uterine activity of 3-5 contractions per 10
minutes is achieved. The maximum allowed dose rate 180 ml/hour for induction of labour.
Active phase: The woman will be included in the study, when the active phase of labour is
established (cervical dilatation ≥ 6 cm, ≥3 contractions per 10 minutes, and rupture of
membranes). Randomisation is performed, and the infusion will be replaced by the trial
solution, which will be either Syntocinon® at the same concentration, or a placebo infusion
which will not contain Syntocinon®:
1. Control group; 10 IE Syntocinon® diluted in 1000 ml 0,9% NaCl infusion
2. Intervention group; 1ml 0,9% NaCl diluted in 1000ml 0,9% NaCl infusion. The infusion
will be continued to achieve uterine activity of 3-5 contractions per 10 minutes.
Maximum allowed dose is 180 ml/hour for induction. The procedure for administration of
the trial solution is identical with the existing procedure.
Complications:
The infusion will be reduced or discontinued at any point of labour, if the following occur:
- Hyperstimulation (>5 contractions per 10 minutes and non-reassuring CTG13). A management
algorithm for this situation is made.
- Uterine contractions lasting 2 minutes or more
- Non-reassuring CTG (recurrent variable decelerations, fetal tachycardia or bradycardia,
minimal to absent baseline variability, late decelerations)
- Suspicion of uterine rupture These conditions will be managed according to the
guidelines of the local delivery wards.
Dystocia:
If there is failure to progress, defined as less than two cm dilation over 4 hours despite
apparently adequate contractions and/or maximal infusion rates (Syntocinon® or placebo), the
project medicine will be replaced with open-labelled Syntocinon® infusion. Stimulation will
be given according to national DSOG guidelines7. Initially 20 ml/hour of 10 IE Syntocinon®
diluted in 1000 ml 0,9% NaCl. The dose rate will be increased every 20 minutes by 20 ml/hour
until appropriate uterine activity of 3-5 contractions per 10 minutes is achieved. The
maximum allowed dose rate is180 ml/hour for induction.
Woman receiving open-labelled Syntocinon® infusion for 4 hours and continuous failure to
progress: Consider caesarean section.
Unconcealment The primary investigator or a nominated deputy will at all time be able to
break the randomisation code and reveal the allocation group, if needed. The Internet Based
Randomisation Programme will provide the primary investigator or a nominated deputy with this
possibility. (A 24/7 availability of the allocation group is thereby provided).
Side effects and risks:
Persistent failure to progress can be expected in 8-46% of the participants in the placebo
group versus 3-17% in the control group. 3 4 5 6 Based on data from the pilot study, the risk
of caesarean section is expected to be 15% in the placebo group versus 22% in the control
group. According to the pilot study and previous studies 3 4 5 6, the maternal and neonatal
complications in the placebo group are expected to be lower than in the control group.
All participants are monitored with continuous electronic fetal heart rate monitoring during
labour to detect complications such as uterine tachysystole and non-reassuring/pathological
fetal heart rate, in accordance with national guidelines.
The personnel of the delivery ward are responsible for registering of adverse reactions and
adverse events.
Following adverse reactions and event will be registered immediately in the electronic
medical journal of the patient:
- Cesarean delivery
- Postpartum hemorrhage >500 ml
- Manual placenta removal
- Rupture of the anale sphincter
- Urine retention
- Neonatal: pH <7,10 and/or Apgar score ≤ 6 at 5 minutes
Following serious adverse reactions and adverse events will be also registered immediately in
the electronic medical journal of the patient:
- Intrauterine dead during labour
- Maternal amniotic fluid emboli or thromboembolic event
- Maternal cardiac arrest
- Maternal Pulmonary edema
- Uterine rupture The women will be followed for at least 3-6 hours postpartum
(termination of project medicine) according current practice on the delivery ward.
The product resume of Syntocinon® will be used as reference to determine whether a Serious
Adverse Reaction is expected or unexpected. Primary investigator or a nominated deputy will
go through the participants medical file 7-30 days postpartum during data management and
Primary investigator will ensure that all relevant information about suspected serious
unexpected adverse reactions that are fatal or life-threatening is recorded and reported as
soon as possible to the competent authorities concerned, and to the Ethics Committee, and in
any case no later than seven days after the knowledge such a case, and that relevant
follow-up information is subsequently communicated within an additional eight days.
Primary investigator will report to the competent authorities concerned and to the Ethics
Committee concerned all other suspected unexpected serious adverse reactions as soon as
possible but within a maximum of 15 days of first knowledge.
;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT02722356 -
Outcomes After the Implementation of a New Oxytocin Protocol
|
N/A |